Hypertension is the most common cardiovascular disease, and it also is the primary dangerous factors which can lead to increased morbidity and mortality of congestive heart failure, stroke, coronary heart disease, renal failure, and aortic aneurysm. Antihypertensive drugs play a key role in the treatment and prevention of hypertension disease. With the deepening of understandings to the pathogenesis of the hypertension, many antihypertensive drugs having good efficacy, for example, such as diuretics, β-acceptor blockers, calcium channel blockers, angiotensin-converting enzyme inhibitor (ACEI, Pooley), Angiotensin II AT1 receptor blockers (ABR, Sartans), are continuously discovered and successfully applied in clinical practices. After years of clinical practice, it can be confirmed that because the kind of drugs can steadily reduce blood pressure and have good efficacy, long action time, good tolerance for patients, particularly, have many advantages in preventing stroke, delaying renal insufficiency of diabetes and non-diabetes nephropathy, improving left ventricular hypertrophy, and protecting target organs while producing no impacts on degradation of bradykinin and synthesis of prostaglandin, thereby not to cause dry cough and angioneurotic edema, AT1 receptor blockers Sartan drugs have been mainstream variety in global antihypertensive drug market. Although Sartan antihypertensive drugs have many advantages, their efficiency for reducing blood pressure is approximately about 50 to 60%, and the drugs have some adverse effects to some extent. Therefore, the development of long acting drugs with a low dosage and having good effect on reducing blood pressure, less adverse effects while having ideal efficacy in treatments of other diseases, e.g., diabetes, and good protective action on target organs, has been a developing direction in hot issue.
Nitrogen monoxide, as a messenger substance and an effect molecule, can have very important physiological functions in mammals, including controls to angiotasis, nerve conduction, hormone secretion, inflammation and immune reactions. In addition, it can also play important roles in regulations to vascular diastolic function, cell adhesion to vascular endothelium and platelet aggregation, cell proliferation of vascular smooth muscle and protections to ischemia-reperfusion injuries. ACE inhibitors have good actions on reducing blood pressure and protecting target organs. By inhibiting the activity of the ACE, on one hand, they can inhibit generations of angiotensin II so as to exert the function; on the other hand, they can work on the inhibition of endogenous peptides, e.g., bradykinin, to result in the increase of the concentration of bradykinin in vivo, so as to enhance the eNOs activity by activating β2-receptors, thereby to promote endothelium-derived hyperpolarizing factor and NO release, thus to exert functions such as NO-mediated vasodilation and platelet aggregation inhibition.
AT1 receptor Losartan antagonists are a kind of novel antihypertensive drugs which are selectively bound to AT1 receptors, and block the actions of Ang II, thereby to result in reduction of blood pressure. However, as compared with ACE inhibitors, AT1 receptor blockers are lack of NO-mediated regulation function. Thus, AT1 acceptor blockers of NO donor type are developed to achieve the dual efficacy of blocking ATI acceptors and enhancing NO functions in vivo, and the type of ATI acceptor blockers can have more effective treating effects on hypertension, while having potential values to treat other cardiovascular diseases. Ligustrazine (Lig) is one of primary chemical ingredients in the rhizomas of umbelliferae plant Ligusticum Chuanxiong Hort and Zingiberaceae plant Curcuma Aromatica Salisb, and the stem of Euphorbiaceae plant Jatropha podagrica Hook. Pharmacological studies proved that the Ligustrazine can act their functions to improve microcirculation, dilate blood vessels and increase blood flow, inhibit platelet aggregation and reduce platelet activity, and can have significant effects on the treatment of cardiovascular disease. Thus, clinically, the Ligustrazine is widely used in treatments of brain stroke, asthma, emphysema, pulmonary heart disease, chronic respiratory failure, adult respiratory distress syndrome and other diseases, and the mechanism primarily includes cleaning free radicals, resisting peroxidization of lipids, protecting crown pulse endothelial, promoting energy metabolism of myocardial cells, resisting fiberization, controlling expressions of apoptosis related genes c-fos and bc1-2, resisting injuries to free radicals, influencing cell factors, calcium antagonism, resisting myocardial hypoxia-complex oxygen injury, resisting myocardial mast caused by anti-vascular tension pigment II (blocking AT1 receptor), expanding vascular, and resisting platelet gathered and thrombogenesis. Ligustrazine AT1 acceptor blockers are developed, which either can effectively enhance the efficacy of the ATI acceptor blockers on resisting high blood pressure, or can effectively protect liver and kidney, while having potential therapeutical implications to other cardiovascular diseases. No relative reports are found in the prior art.